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Parachlorophenylalanine
Parachlorophenylalanine (p-Chlorophenylalanine, PCPA) aka Fenclonine is a synthetic amino acid which acts as a selective and irreversible inhibitor of tryptophan hydroxylase, which is a rate-limiting enzyme in the biosynthesis of serotonin.Jéquier E, Lovenberg W, Sjoerdsma A. Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Molecular Pharmacology. 1967 May;3(3):274-8. PMID 6037686 Fenclonine consequently depletes serotonin in the body and reduces its actions, acting as an indirect serotonin antagonist. It is used in scientific research to investigate the effects of serotonin depletion on behaviour.O'Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berlin). 2007 Jun;192(3):357-71. PMID 17318507 See also * Phenylalanine * α-Methyltyrosine * Serotonin antagonists References Further reading Books *Harvey, B. H., Naciti, C., Brand, L., & Stein, D. J. (2004). Serotonin and Stress: Protective or Malevolent Actions in the Biobehavioral Response to Repeated Trauma? New York, NY: New York Academy of Sciences. *Boranic, M., Pericic, D., Poljak-Blazi, M., Sverko, V., & Marotti, T. (1987). Suppression of immune response in rats by stress and drugs interfering with metabolism of serotonin. New York, NY: New York Academy of Sciences. Papers Alexander, G. J., & Kopeloff, L. M. (1976). Additive effect of 5-hydroxytryptophan and p-chlorophenylalanine in preventing audiogenic seizures in inbred mice: Psychopharmacology Communications Vol 2(5-6) 1976, 379-390. *Alexander, G. J., & Kopeloff, L. M. (1978). Anticonvulsive effect of p-chlorophenylalanine in mice on a low magnesium diet: Pharmacology, Biochemistry and Behavior Vol 8(3) Mar 1978, 291-293. *Alpern, H. P., & Jackson, S. J. (1978). Short-term memory: A neuropharmacologically distinct process: Behavioral & Neural Biology Vol 22(2) Feb 1978, 133-146. *Altenor, A., & DeYoe, E. A. (1977). The effects of {dl}-p-chlorophenylalanine on learned helplessness in the rat: Behavioral & Neural Biology Vol 20(1) May 1977, 111-115. *Amar, A., & Sanyal, A. K. (1981). Immobilization stress in rats: Effect on rectal temperature and possible role of brain monoamines in hypothermia: Psychopharmacology Vol 73(2) Apr 1981, 157-160. *Annerbrink, K., Olsson, M., Melchior, L. K., Hedner, J., & Eriksson, E. (2003). Serotonin depletion increases respiratory variability in freely moving rats: implications for panic disorder: International Journal of Neuropsychopharmacology Vol 6(1) Mar 2003, 51-56. *Armario, A., Marti, O., & Gavalda, A. (1992). Negative feedback of corticosterone on the pituitary-adrenal axis is maintained after inhibition of serotonin synthesis with parachlorophenylalanine: Brain Research Bulletin Vol 28(6) Jun 1992, 915-918. *Armario, A., Marti, O., Gavalda, A., & Lopez-Calderon, A. (1993). Evidence for the involvement of serotonin in acute stress-induced release of luteinizing hormone in the male rat: Brain Research Bulletin Vol 31(1-2) 1993, 29-31. *Baker, G. B., Martin, I. L., Coutts, R. T., & Benderly, A. (1982). Para-chlorophenylethylamine in brains of rats treated with a monoamine oxidase inhibitor and p-chlorophenylalanine: Progress in Neuro-Psychopharmacology & Biological Psychiatry Vol 6(4-6) 1982, 343-346. *Baker, M. W., Vohra, M. M., & Croll, R. P. (1993). Serotonin depletors, 5,7-dihydroxytryptamine and p-chlorophenylalanine, cause sprouting in the CNS of the adult snail: Brain Research Vol 623(2) Oct 1993, 311-315. *Balander, R. J., Bursian, S. J., Van Krey, H. P., & Siegel, P. B. (1984). Mating behavior and brain biogenic amine concentrations in chickens treated with parachlorophenylalanine (PCPA): Physiology & Behavior Vol 32(4) Apr 1984, 603-607. *Beiko, J., Candusso, L., & Cain, D. P. (1997). The effect of nonspatial water maze pretraining in rats subjected to serotonin depletion and muscarinic receptor antagonism: A detailed behavioural assessment of spatial performance: Behavioural Brain Research Vol 88(2) Nov 1997, 201-211. *Beninger, R. J., & Phillips, A. G. (1979). Possible involvement of serotonin in extinction: Pharmacology, Biochemistry and Behavior Vol 10(1) Jan 1979, 37-41. *Bodnar, R. J., & et al. (1984). Reductions in pain thresholds and morphine analgesia following intracerebroventricular parachlorophenylalanine: Pharmacology, Biochemistry and Behavior Vol 21(1) Jul 1984, 79-84. *Bond, N. W. (1986). Prenatal alcohol exposure and offspring hyperactivity: Effects of para-chlorophenylalanine and methysergide: Neurobehavioral Toxicology & Teratology Vol 8(6) Nov-Dec 1986, 667-673. *Boranic, M., Pericic, D., Poljak-Blazi, M., Sverko, V., & et al. (1987). Suppression of immune response in rats by stress and drugs interfering with metabolism of serotonin: Annals of the New York Academy of Sciences Vol 496 May 1987, 485-491. *Borbely, A. A., Neuhaus, H. U., & Tobler, I. (1981). Effect of p-chlorophenylalanine and tryptophan on sleep, EEG and motor activity in the rat: Behavioural Brain Research Vol 2(1) Jan 1981, 1-22. *Boren, J. L., Suarez, S. D., & Gallup, G. G. (1981). p-Chloroamphetamine: Effects on tonic immobility, activity, and temperature in chickens: Journal of Comparative and Physiological Psychology Vol 95(6) Dec 1981, 991-1002. *Buchanan, C. P., Shrier, E. M., & Hill, W. L. (1994). Time-dependent effects of PCPA on social aggression in chicks: Pharmacology, Biochemistry and Behavior Vol 49(3) Nov 1994, 483-488. *Butcher, R. E., & et al. (1977). Induced PKU in rats: Effects of age and melatonin treatment: Pharmacology, Biochemistry and Behavior Vol 7(2) Aug 1977, 129-133. *Buterbaugh, G. G. (1977). A role for central serotonergic systems in the pattern and intensity of the convulsive response of rats to electroshock: Neuropharmacology Vol 16(10) Oct 1977, 707-709. *Calvino, B. (1990). Hypoalgesia induced by counter-irritation is not affected by pCPA pretreatment: Pharmacology, Biochemistry and Behavior Vol 35(3) Mar 1990, 731-734. *Cervantes, M., Ruelas, R., & Beyer, C. (1983). Serotonergic influences on EEG synchronization induced by milk drinking in the cat: Pharmacology, Biochemistry and Behavior Vol 18(6) Jun 1983, 851-855. *Cespuglio, R., Calvo, J.-M., Musolino, R., & Valatx, J.-L. (1977). Phasic activity in the rat: Physiology & Behavior Vol 19(5) Nov 1977, 589-596. *Chamove, A. S. (1984). Analysis of learning in retarded monkeys: Journal of Mental Deficiency Research Vol 28(1) Mar 1984, 21-41. *Chance, W. T., von Meyenfeldt, M., & Fischer, J. E. (1982). Delay of cancer anorexia following intraventricular injection of para-chlorophenylalanine: Pharmacology, Biochemistry and Behavior Vol 17(5) Nov 1982, 1043-1048. *Coderre, T. J., & Rollman, G. B. (1984). Stress analgesia: Effects of PCPA, yohimbine, and naloxone: Pharmacology, Biochemistry and Behavior Vol 21(5) Nov 1984, 681-686. *Colasanti, B. K. (1977). Involvement of brain biogenic amines in the electroencephalographic and behavioral effects of morphine in post-addict rats: Neuropharmacology Vol 16(4) Apr 1977, 235-240. *Contreras, S., Alvarado, R., & Mardones, J. (1990). Effects of p-chlorophenylalanine on the voluntary consumption of ethanol, water and solid food by UChA and UChB rats: Alcohol Vol 7(5) Sep-Oct 1990, 403-407. *Cooley, J. E., Villarosa, G. A., Lombardo, T. W., Moss, R. A., & et al. (1990). Effect of pCPA on nicotine-induced analgesia: Pharmacology, Biochemistry and Behavior Vol 36(2) Jun 1990, 413-415. *Copenhaver, J. H., Schalock, R. L., & Carver, M. J. (1978). Para-chloro-D,L-phenylalanine induced filicidal behavior in the female rat: Pharmacology, Biochemistry and Behavior Vol 8(3) Mar 1978, 263-270. *Copenhaver, J. H., Schalock, R. L., Johnson, L., Stull, T., & et al. (1989). Relationship between preexposure to prey and PCPA-induced filicidal activity in Sprague-Dawley rats: Physiology & Behavior Vol 45(2) Feb 1989, 343-346. *Corum, C. R., & Thurmond, J. B. (1978). Effects of PCPA and selective REM sleep deprivation on rotorod performance and open-field behavior in the rat: Bulletin of the Psychonomic Society Vol 11(4) Apr 1978, 251-254. *Coscina, D. V., Daniel, J., & Warsh, J. J. (1978). Potential non-serotonergic basis of hyperphagia elicited by intraventricular p-chlorophenylalanine: Pharmacology, Biochemistry and Behavior Vol 9(6) Dec 1978, 791-797. *Dasari, S., Viele, K., Turner, A. C., & Cooper, R. L. (2007). Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in drosophila melanogaster: European Journal of Neuroscience Vol 26(2) Jul 2007, 424-438. *DeLisi, L. E., & et al. (1982). p-Chlorophenylalanine trials in schizophrenic patients: Biological Psychiatry Vol 17(4) Apr 1982, 471-477. *Dourish, C. T., Hutson, P. H., & Curzon, G. (1986). Para-chlorophenylalanine prevents feeding induced by the serotonin agonist-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT): Psychopharmacology Vol 89(4) Jul 1986, 467-471. *Dringenberg, H. C., Hargreaves, E. L., Baker, G. B., Cooley, R. K., & et al. (1995). p-chlorophenylalanine-induced serotonin depletion: Reduction in exploratory locomotion but no obvious sensory-motor deficits: Behavioural Brain Research Vol 68(2) Jun 1995, 229-237. *Dryden, S., Frankish, H. M., Wang, Q., & Williams, G. (1996). Increased feeding and neuropeptide Y (NPY) but not NPY mRNA levels in the hypothalamus of the rat following central administration of the serotonin synthesis inhibitor p-chlorophenylalanine: Brain Research Vol 724(2) Jun 1996, 232-237. *El-Yousef, M. K., Steranka, L., & Sanders-Bush, E. (1977). Rapid tolerance to the motor effects of p-chloroamphetamine in rats: Psychopharmacology Vol 55(2) 1977, 109-114. *Emery, D. E., & Moss, R. L. (1984). p-Chlorophenylalanine alters pacing of copulation in female rats: Pharmacology, Biochemistry and Behavior Vol 20(3) Mar 1984, 337-341. *Fernandez-Guasti, A., & Lopez-Rubalcava, C. (1995). Action of ipsapirone and 8-OH-DPAT on exploratory behavior in hamsters (Mesocricetus auratus): Effects of antagonists and p-CPA: Pharmacology, Biochemistry and Behavior Vol 50(3) Mar 1995, 375-382. *File, S. E. (1977). Effects of parachlorophenylalanine and amphetamine on habituation of exploration: Pharmacology, Biochemistry and Behavior Vol 6(2) Feb 1977, 151-156. *Fitzgerald, R. E., Oettinger, R., & Battig, K. (1985). Reduction of nicotine-induced hyperactivity by pCPA: Pharmacology, Biochemistry and Behavior Vol 23(2) Aug 1985, 279-284. *Fjalland, B. (1979). Antagonism of apomorphine-induced hyperthermia in MAOI-pretreated rabbits as a sensitive model of neuroleptic activity: Psychopharmacology Vol 63(2) 1979, 119-123. *Frankel, D., Khanna, J. M., Kalant, H., & LeBlanc, A. E. (1978). Effect of p-chlorophenylalanine on the acquisition of tolerance to the hypothermic effects of ethanol: Psychopharmacology Vol 57(3) 1978, 239-242. *Frankel, D., Khanna, J. M., Kalant, H., & Leblanc, A. E. (1978). Effect of p-chlorophenylalanine on the loss and maintenance of tolerance to ethanol: Psychopharmacology Vol 56(2) 1978, 139-143. *Fuchs, V., Burbes, E., Coper, H., & Wagner, N. (1983). Significance of biogenic amines for opioid-induced locomotor activity in rats: Drug and Alcohol Dependence Vol 12(3) Nov 1983, 233-242. *Garrigou, D., & Blozovski, D. (1980). Parachlorophenylalanine and atropine influences on theta activity in the young rat: Behavioral & Neural Biology Vol 29(3) Jul 1980, 365-371. *Gibbons, J. L., Barr, G. A., Bridger, W. H., & Leibowitz, S. F. (1978). Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats: Pharmacology, Biochemistry and Behavior Vol 9(1) Jul 1978, 91-98. *Goodrich, C., & Wilk, C. (1981). Temperature preferences and the effect of changes in serotonin in maturing mice: Physiology & Behavior Vol 26(6) Jun 1981, 1041-1047. *Gratton, A. (1982). Time course analysis of para-chlorophenylalanine induced suppression of self-stimulation behavior: Pharmacology, Biochemistry and Behavior Vol 17(4) Oct 1982, 597-602. *Guillemot, J.-P., Lepore, F., & Telner, J. (1979). Effects of serotonin on sensitivity and reactivity during various states of vigilance: Physiology & Behavior Vol 22(2) Feb 1979, 383-386. *Harder, J. A., & Kelly, M. E. (1997). The effect of several putative cognitive enhancers on a water maze acquisition deficit produced by pCPA + scopolamine combination treatment: Pharmacology, Biochemistry and Behavior Vol 56(4) Apr 1997, 657-661. *Harder, J. A., Kelly, M. E., Cheng, C. H. K., & Costall, B. (1996). Combined pCPA and muscarinic antagonist treatment produces a deficit in rat water maze acquisition: Pharmacology, Biochemistry and Behavior Vol 55(1) Sep 1996, 61-65. *Haskett, C., & Mueller, K. (1987). The effects of serotonin depletion on the voltammetric response to amphetamine: Pharmacology, Biochemistry and Behavior Vol 28(3) Nov 1987, 381-384. *Honma, K.-i., Watanabe, K., & Hiroshige, T. (1979). Effect of parachlorophenylalanine and 5,6-dihydroxytryptamine on the free-running rhythms of locomotor activity and plasma corticosterone in the rat exposed to continuous light: Brain Research Vol 169(3) Jun 1979, 531-544. *Hughes, R. A. (1986). P-chlorophenylalanine attenuates tonic immobility duration in chickens: Physiology & Behavior Vol 36(3) 1986, 427-430. *Jackson, H. F., & Broadhurst, P. L. (1982). The effects of parachlorophenylalanine and stimulus intensity on open-field test measures in rats: Neuropharmacology Vol 21(12) Dec 1982, 1279-1282. *Jakala, P., Servio, J., Riekkinen, Jr., & Riekkinen, P. J. (1993). Effects of p-chlorophenylalanine and methysergide on the performance of a working memory task: Pharmacology, Biochemistry and Behavior Vol 44(2) Feb 1993, 411-418. *Jakala, P., Sirvio, J., Jolkkonen, J., Riekkinen, P., & et al. (1992). The effects of p-chlorophenylalanine-induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task: Behavioural Brain Research Vol 51(1) Oct 1992, 29-40. *Johnston, H. M., Payne, A. P., Gilmore, D. P., & Wilson, C. A. (1990). Neonatal serotonin reduction alters the adult feminine sexual behaviour of golden hamsters: Pharmacology, Biochemistry and Behavior Vol 35(3) Mar 1990, 571-575. *Jones, T. A., Lawrence, A. F., & Bickford, R. G. (1983). Serotonin depletion prevents electrocortical synchronization following acute midbrain deactivation: Electroencephalography & Clinical Neurophysiology Vol 55(2) Feb 1983, 203-211. *Kalkman, H. O. (1990). Discriminative stimulus properties of 8-OH-DPAT in rats are not altered by pretreatment with para-chlorophenylalanine: Psychopharmacology Vol 101(1) May 1990, 39-42. *Kayser, C., & Hildwein, G. (1977). The circadian rhythm of rat motor activity and the effect of brain monoamine inhibitors (PCPA and nialamide): Chronobiologia Vol 4(1) Jan-Mar 1977, 18-37. *Keele, N. B. (2001). Phenytoin inhibits isolation-induced aggression specifically in rats with low serotonin: Neuroreport: For Rapid Communication of Neuroscience Research Vol 12(6) May 2001, 1107-1112. *Knutson, J. F., & et al. (1979). Influence of PCPA, shock level, and home-cage conditions on shock-induced aggression: Physiology & Behavior Vol 23(5) Nov 1979, 897-907. *Kohler, C., & Lorens, S. A. (1978). Open field activity and avoidance behavior following serotonin depletion: A comparison of the effects of parachlorophenylalanine and electrolytic midbrain raphe lesions: Pharmacology, Biochemistry and Behavior Vol 8(3) Mar 1978, 223-233. *Korpela, S. R., & Sandnabba, N. K. (1998). The relationship between aggressive and sexual behavior in male mice: Effects of testosterone and parachlorophenylalanine: Aggressive Behavior Vol 24(5) 1998, 367-377. *Kusumi, I., Mikuni, M., & Takahashi, K. (1991). Effect of subchronic antidepressants administration on serotonin-stimulated phosphoinositide hydrolysis in para-chlorophenylalanine-treated rat hippocampal slices: Progress in Neuro-Psychopharmacology & Biological Psychiatry Vol 15(3) 1991, 393-403. *Laguzzi, R. F. (1982). Effects of serotonin synthesis inhibition on sleep in hippocampectomized rats: Brain Research Vol 240(1) May 1982, 175-177. *Lee, H. K., & et al. (1977). Mechanisms of amitriptyline induced hypothermia in the rat: Pharmacology, Biochemistry and Behavior Vol 7(2) Aug 1977, 159-165. *Lenke, R. (1988). Hormonal control of sleep-appetitive behaviour and diurnal activity rhythms in the cleaner wrasse Labroides dimidiatus (Labridae, Teleostei): Behavioural Brain Research Vol 27(1) Jan 1988, 73-85. *Li, E. T., & Anderson, G. H. (1984). 5-Hydroxytryptamine: A modulator of food composition but not quantity? : Life Sciences Vol 34(25) Jun 1984, 2453-2460. *Li, H., & Satinoff, E. (1992). Effects of p-chlorophenylalanine on thermoregulation and sleep in rats: Brain Research Vol 569(1) Jan 1992, 46-56. *Lyness, W. H., & Smith, F. L. (1992). Influence of dopaminergic and serotonergic neurons on intravenous ethanol self-administration in the rat: Pharmacology, Biochemistry and Behavior Vol 42(1) May 1992, 187-192. *Maekawa, F., & Yamanouchi, K. (1996). Effect of deprivation of serotonin by rho -chlorophenylalanine on induction and maintenance of pseudopregnancy in female rats: Brain Research Bulletin Vol 39(5) 1996, 317-321. *Maickel, R. P., Light, K. E., & Zabik, J. E. (1982). Differential activity of enantiomers of amphetamine in rats: Neuropharmacology Vol 21(12) Dec 1982, 1323-1327. *Malick, J. B., Doren, E., & Barnett, A. (1977). Quipazine-induced head-twitch in mice: Pharmacology, Biochemistry and Behavior Vol 6(3) Mar 1977, 325-329. *Marsden, C. A., & Curzon, G. (1977). Effects of p-chlorophenylalanine and !a-methyltryptophan on behaviour and brain 5-hydroxyindoles: Neuropharmacology Vol 16(7-8) Jul-Aug 1977, 489-494. *Matsumoto, T., Kondo, Y., Sachs, B. D., & Yamanouchi, K. (1997). Effects of p-chlorophenylalanine on reflexive and noncontact penile erections in male rats: Physiology & Behavior Vol 61(2) Feb 1997, 165-168. *Matte, A. C., & Tornow, H. (1978). Parachlorophenylalanine produces dissociated effects on aggression "emotionality" and motor activity: Neuropharmacology Vol 17(8) Aug 1978, 555-558. *Mattingly, B. A., Chandler, H., Applegate, E. B., & Brunelle, M. (1984). Activity during a conditioned aversive stimulus in rats treated with para-chlorophenylalanine: Psychological Record Vol 34(3) Sum 1984, 389-396. *Miliaressis, E. (1977). Serotonergic basis of reward in median raphe of the rat: Pharmacology, Biochemistry and Behavior Vol 7(2) Aug 1977, 177-180. *Mueller, K., & Nyhan, W. L. (1982). Pharmacologic control of pemoline induced self-injurious behavior in rats: Pharmacology, Biochemistry and Behavior Vol 16(6) Jun 1982, 957-963. *Munoz-Castaneda, J. R., Montilla, P., Padillo, F. J., Bujalance, I., Munoz, M. C., Muntane, J., et al. (2006). Role of serotonin in cerebral oxidative stress in rats: Acta Neurobiologiae Experimentalis Vol 66(1) 2006, 1-6. *Murphy, D. L., Campbell, I. C., & Costa, J. L. (1978). 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